Chondrocytes are cells specific to articular cartilage. The isolation and cultivation of chondrocytes is a standard procedure, which has been undertaken for more than 10 years. Under two-dimensional culture conditions in cell culture vessels, chondrocytes dedifferentiate to fibroblast-like cells. During the dedifferentiation they lose their typical properties (grade of differentiation, cell form, synthesis of cartilage-specific matrix components), which are essential for physiology and biomechanics of cartilage.
For many years there have been attempts to transplant dedifferentiated chondrocytes grown under two-dimensional culture conditions into human joint defects. Transplantation of cells grown in culture provides another method of introducing a new cell population into chondral and osteochondral defects. The procedure uses arthroscopy to take a biopsy from a healthy, less loaded area of articular cartilage. Enzymatic digestion of the harvested tissue releases the cells that are sent to a laboratory where they are grown. Once cultivated, they are injected during a more open and extensive knee procedure into areas of defective cartilage in an attempt to facilitate the repair of damaged tissue.
The technique of autologous chondrocyte transplantation is very complex and requires postoperative immobilization of the patient. The surgical site cannot bear load post surgery because the transplanted chondrocytes have to reach their original biological state (redifferentiation of in vitro dedifferentiated cells), then have to anchor to the defect, synthesize the cartilage-specific matrix and rebuild a new cartilage.
In the procedure of mosaicplasty (autologous cartilage transplantation), cartilage-bone cylinders are removed from non-load-bearing joint areas of the patient and transplanted into the defect. This method shows good clinical results including a good load capacity of the operated knee-joint, but is only applicable to small cartilage defects due to the limited availability of autologous osteochondral cylinders. Classical operation techniques, which do not use cartilage or chondrocyte transplantation (abrasion, debridement, Pridie-drilling), result only in a defect repair with fibrous, less load-bearing tissue unfortunately. Additionally, repeated treatment is necessary as this tissue degenerates over time.
Osteochondral transplantation or mosaicplasty involves excising all injured or unstable tissue from the articular defect and creating cylindrical holes in the base of the defect and underlying bone. These holes are filled with autologous cylindrical plugs of healthy cartilage and bone in a mosaic fashion. The osteochondral plugs are harvested from a lower weight-bearing area of lesser importance in the same joint. Reports of results of osteochondral plug autografts in a small number of patients indicate that they decrease pain and improve joint function, however, long-term results have not been reported. Factors that can compromise the results include donor site morbidity, effects of joint incongruity on the opposing surface of the donor site, damage to the chondrocytes at the articular margins of the donor and recipient sites during preparation and implantation, and collapse or settling of the graft over time. The limited availability of sites for harvest of osteochondral autografts restricts the use of this approach to treatment of relatively small articular defects and the healing of the chondral portion of the autograft to the adjacent articular cartilage remains a concern.
As previously noted, transplantation of cells grown in culture provides another method of introducing a new cell population into chondral and osteochondral defects. Carticel® is a commercial process to culture the patient's own cartilage cells for use in the repair of cartilage defects in the knee joint marketed by Genzyme Biosurgery in the United States and Europe. The procedure uses arthroscopy to take a biopsy from a healthy, less loaded area of articular cartilage. Enzymatic digestion of the harvested tissue releases the cells that are sent to a laboratory where they are grown for a period ranging from 2-5 weeks to achieve a 10 fold increase in cell mass. Once cultivated, the autologous cells are injected during an open and extensive knee procedure into areas of defective cartilage where it is hoped that they will facilitate the repair of damaged tissue. An autologous periosteal flap with cambium layer facing down is used to seal the transplanted cells in place and act as a mechanical barrier. Fibrin glue is used to seal the edges of the flap. This technique preserves the subchondral bone plate. Proponents of this procedure report that it produces satisfactory results, including the ability to return to demanding physical activities, in more than 80% of patients and that biopsy specimens of the tissue in the graft sites show hyaline-like cartilage repair. However, long term studies of this procedure in rabbits and dogs showed limited success and showed degradation at the implant site. The original study report has been criticized for not being a prospective controlled randomized study and for lack of quantitative or mechanical data. Of interest, a 14 year follow-up of a similar patient group that underwent diagnostic arthroscopy in combination with one of several treatments (removal of bone bodies, shaving, Pridie drilling) had good to excellent knee function in 78% of the patients. Thus, further studies are needed to assess the function and durability of the new tissue to determine whether it improves joint function and delays or prevents joint degeneration.
As with the perichondrial graft, patient/donor age may compromise the success of this procedure as the chondrocyte population decreases with increasing age. Disadvantages to this procedure include the need for two separate surgical procedures, potential damage to surrounding cartilage when the periosteal patch is sutured in place, the requirement of demanding microsurgical techniques, and the expensive cost of the procedure which is currently not covered by insurance.
The use of implants for cartilage defects is much more limited than that for bone defects. Aside from the fresh allograft implants and autologous implants, U.S. Pat. No. 6,110,209 issued Nov. 5, 1998 shows the use of an autologous articular cartilage cancellous bone paste to fill arthritic defects. The surgical technique is arthroscopic and includes debriding (shaving away loose or fragmented articular cartilage), followed by morselizing the base of the arthritic defect with an awl until bleeding occurs. An osteochondral graft is then harvested from the inner rim of the intercondylar notch using a trephine. The graft is then morselized in a bone graft crusher, mixing the articular cartilage with the cancellous bone. The paste is then pushed into the defect and secured by the adhesive properties of the bleeding bone. The paste can also be mixed with a cartilage stimulating factor, a plurality of cells, or a biological glue. All patients are kept non-weight bearing for four weeks and used a continuous passive motion machine for six hours each night. Histologic appearance of the biopsies have mainly shown a mixture of fibrocartilage with hyaline cartilage. Concerns associated with this method are harvest site morbidity and availability, similar to the mosaicplasty method.
U.S. Pat. No. 6,379,367 issued Apr. 30, 2002 discloses a plug with a base membrane, a control plug, and a top membrane which overlies the surface of the cartilage covering the defective area of the joint.
U.S. Pat. No. 6,488,033 issued Dec. 3, 2002 discloses an allograft plug with a cartilage cap which is surface contour matched to the surface of a condyle defect area which is to be replaced. The allograft plug is transplanted in an interference fit within the cavity site which remains after a condylar defect is removed from a patients condyle.
The present implant and method differs from the above prior art in that it is directed to allograft chondrocyte transplantation on an allograft cancellous bone carrier to provide an implant for cartilage transplantation.